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Variation in tau isoform expression in different brain regions and disease states

Lookup NU author(s): Dr Christopher Morris

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Abstract

Progressive supranuclear palsy (PSP) is the most common atypical parkinsonian disorder. Abnormal tau inclusions, in selected regions of the brain, are a hallmark of the disease and the H1 haplotype of MAPT, the gene encoding tau, is the major risk factor in PSP. A 3-repeat and 4-repeat (4R) tau isoform ratio imbalance has been strongly implicated as a cause of disease. Thus, understanding tau isoform regional expression in disease and pathology-free states is crucial to elucidating the mechanisms involved in PSP and other tauopathies. We used a tau isoform-specific fluorescent assay to investigate relative 4R-tau expression in 6 different brain regions in PSP cases and healthy control samples. We identified a marked difference in 4R-tau relative expression, across brain regions and between MAPT haplotypes. Highest 4R-tau expression levels were identified in the globus pallidus compared with pons, cerebellum, and frontal cortex. 4R-tau expression levels were related to the MAPT H1 and H1c haplotypes. Similar regional variation was seen in PSP case and in control samples. (C) 2013 Elsevier Inc. All rights reserved.


Publication metadata

Author(s): Majounie E, Cross W, Newsway V, Dillman A, Vandrovcova J, Morris CM, Nalls MA, Ferrucci L, Owen MJ, O'Donovan MC, Cookson MR, Singleton AB, de Silva R, Morris HR

Publication type: Article

Publication status: Published

Journal: Neurobiology of Aging

Year: 2013

Volume: 34

Issue: 7

Pages: 1922.e7-1922.e12

Print publication date: 01/07/2013

Online publication date: 19/02/2013

Acceptance date: 22/01/2013

ISSN (print): 0197-4580

ISSN (electronic): 1558-1497

Publisher: Elsevier

URL: http://dx.doi.org/10.1016/j.neurobiolaging.2013.01.017

DOI: 10.1016/j.neurobiolaging.2013.01.017


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Funding

Funder referenceFunder name
PSP (Europe) Association
Alzheimer's Research Trust, Brains for Dementia Research Project
Alzheimer's Society
National Institute for Health Research (NIHR) Newcastle Biomedical Research Centre based at Newcastle upon Tyne Hospitals NHS Foundation Trust
Newcastle University
G0501560UK Medical Research Council
G0400074UK Medical Research Council
Z01 AG000932-03Intramural Research Program of the National Institute on Aging, National Institutes of Health, Department of Health and Human Services

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